35 replies to this topic

[Diesel]

I was taking Venlafaxine (150 mg XR) and Clomipramine (150 mg) daily for over a year for severe depression. I quit taking them. Ended up with a very bad case of blunted affect, chronic fatigue, anhedonia and loss of libido. I've been taking Rasagiline and LDN to combat this, but they only improved my anhedonia, depression and fatigue. My libido was still non-existent and I still had no emotions. I was pushed into social isolation for the longest time.

My regimen before adding MSM is:

-Metformin: 1g ER morning, 1g IR night. (Improves the chronic fatigue aspect significantly)
-LDN: 2.5 mg (For the chronic fatigue and anhedonia)
-Rasagiline 0.5 mg (For anhedonia and depression control)
-Melatonin 1.5 mg (For bad sleep, instead of Pregabalin)

-Multivitamins/minerals: zinc, copper, B-complex, selenium 50mcg, vitamin A/D/C, magnesium, manganese, and Iron.

This regimen had been only effective for anhedonia and depression. So, my only problems were blunted affect and loss of libido.

Recently, I have been suffering from a bad joint arthritis. I was taking NSAIDs for it, but since I don't want to be on them chronically, I decided to started taking 5g of MSM (methylsulfonylmethane) instead. Every time I took it, I noticed a definite improvement in blunted affect and libido. Since it'd been a week on it back then, I decided to up the dose to 10g and suddenly I'm enjoying music for the first time in over a year and feeling emotions, and my libido is 25% back to normal. However, the effects only last for 6 hours then I slowly return to my zombie self.

I can't find any research on its effect on neurochemistry, but it DOES something! I also came across a couple of posts of people who had the same reaction, so I decided to post about my own reaction to document my journey. This is my 10th day on it (7 days on 5g, 3 days on 10g. I'm on the same regimen + MSM, obviously).

I have tried SJW and Ginkgo Biloba in the past and they were not effective. Tianeptine made me outright depressed. Maybe I can re-visit SJW and Ginkgo now on MSM? I wonder if its effect can become permanent after facilitation of 5HT1A resensitization.

Edited by Diesel, 18 February 2018 - 02:25 PM.

[Diesel]

Shouldn't SJW + Pindolol/Propranolol, theoretically, be an effective combination in the long term for 5HT1A?

SJW increasing postsynaptic 5HT1A receptor density, and Propranolol antagonizing the presynaptic receptors causing an eventual upregulation of those autoreceptors?

At first, it should make the problem even worse since disinhibiting serotonin release would activate the postsynaptic receptors even more and cAMP inhibiton. But, eventually, the autoreceptors should upregulate in response to antagonism. SJW would counteract the postsynaptic downregulation that would have been induced by serotonin release due to presynpatic antagonism.

After a while (that could be long, mind you), shouldn't we end up with both the pre- and post-synaptic 5HT1A receptor upregulated? and then we can safely just quit Pindolol/Propranolol and SJW.

What about inhibiting VMAT-2 just for a short while? Vincamine comes to mind. Hell, even Reserpine if one is desperate enough. This would cause monoamine depletion which could, on paper, reset 5HT1Ar. DA/NE depletion and depression could be managed by a selective MAO-B inhibitor. After that, we withdraw from Vincamine and viola.

Thing is, I don't have access to Berberine, so I keep coming up with such theories in case MSM never leaves a permanent effect.

Edited by Diesel, 18 February 2018 - 08:54 PM.

[Voulezvous]

I can't comment scientifically, but I have heard anecdotally about benefits of supplementing dietary sulphur as MSM. I just did a cursory search looking for drawbacks and the only thing I saw (not trying very hard, but 2+ pages of search results) was a possible risk of deficiency of something called molybdenum. I've never heard of molybdenum. Another quick search told me it is a chemical element on the long list of essential trace elements.

 

SO, I checked the label on the mineral blend I take, basically just special dirt in water approved for human consumption. There it is in alphabetical order

 

Fulvic/Bio-Mass Minerals, Humic/Bio-Mass Minerals Contains over 70 naturally occurring plant derived minerals, trace elements, vitamins, and amino acids in an unaltered ionic solution. Fulvic/Humic Minerals: Antimony, Barium, Beryllium, Bismuth, Boron, Bromine, Cadmium, Calcium, Carbon, Cerium, Cesium, Chloride, Chromium, Cobalt, Copper, Dysprosium, Erbium, Europium, Fluorine, Gadolinium, Gallium, Germanium, Gold, Hafnium, Holmium, Indium, Iodine, Iridium, Iron, Lanthanum, Lithium, Lutetium, Magnesium, Manganese, Molybdenum, Neodymium, Nickel, Niobium, Osmium, Palladium, Phosphorous, Platinum, Potassium, Praseodymium, Rhenium, Rhodium, Rubidium, Ruthenium, Samarium, Scandium, Selenium, Silicon, Silver, Sodium, Strontium, Sulfur, Tantalum, Tellurium, Terbium, Thulium, Thorium, Tin, Titanium, Tungsten, Vanadium, Ytterbium, Yttrium, Zinc, Zirconium. Amino Acids: Alanine, Glutamic Acid, Glycine, Histidine, Isoleucine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Valine. Vitamins: A, E, B1, B2, B3, B6, B12. Other Ingredients: Purified Reverse Osmosis De-ionizedCarbon Filtered Water. Daily value not established. *Percent daily values are based on a 2000 calorie diet.

 

To me, taking these minerals is like a safety net. I wish I kept track of all the times I've read about certain nutrients needing a speck of something or other, looked at the label, and there it is. I don't know that it's a decent ratio, but it is more than 0:1. 

 

My point being, MSM seems like a good idea even if you don't track down the neuroscience of it. It's possible no one knows (yet) 

-and you might want to consider a trace mineral supplement for this and many other reasons. I'm always wishing there were more studies on them. When I look for information I find a lot of skepticism due to lack of empirical data.

 

 

 

 

 

 

 

 

 

 

 

Shouldn't SJW + Pindolol/Propranolol, theoretically, be an effective combination in the long term for 5HT1A?

SJW increasing postsynaptic 5HT1A receptor density, and Propranolol antagonizing the presynaptic receptors causing an eventual upregulation of those autoreceptors?

At first, it should make the problem even worse since disinhibiting serotonin release would activate the postsynaptic receptors even more and cAMP inhibiton. But, eventually, the autoreceptors should upregulate in response to antagonism. SJW would counteract the postsynaptic downregulation that would have been induced by serotonin release due to presynpatic antagonism.

After a while (that could be long, mind you), shouldn't we end up with both the pre- and post-synaptic 5HT1A receptor upregulated? and then we can safely just quit Pindolol/Propranolol and SJW.

What about inhibiting VMAT-2 just for a short while? Vincamine comes to mind. Hell, even Reserpine if one is desperate enough. This would cause monoamine depletion which could, on paper, reset 5HT1Ar. DA/NE depletion and depression could be managed by a selective MAO-B inhibitor. After that, we withdraw from Vincamine and viola.

Thing is, I don't have access to Berberine, so I keep coming up with such theories in case MSM never leaves a permanent effect.

 

[ThreeKings12341]

hmm. thats nice. before msm. were u able to feel any emotion at all? i suffer from complete emotional numbness.

[Voulezvous]

I don't want to be a pest- I'm no more of an expert than yesterday, but if sulfur affects molybendum, and it's this crucial, please keep balance in mind. 

 

https://www.seekingh...um-100-capsules

 

https://io9.gizmodo....hear-1718443869

[Diesel]

hmm. thats nice. before msm. were u able to feel any emotion at all? i suffer from complete emotional numbness.

No. I was completely numbed up. The only thing I was able to feel from time to time is anger and irritability.

 

I don't want to be a pest- I'm no more of an expert than yesterday, but if sulfur affects molybendum, and it's this crucial, please keep balance in mind. 

 

https://www.seekingh...um-100-capsules

 

https://io9.gizmodo....hear-1718443869

I listened to your advice. I added Molybdenum to my stack.

[ThreeKings12341]

thx Diesel , would u be so kind and tell me the product u are using? pls

 

how are the effects today?

[Diesel]

thx Diesel , would u be so kind and tell me the product u are using? pls

 

how are the effects today?

I'm using a locally produced one. You should find something that contains at least 5g per pill, or instead go for bulk.

The effects are still consistent as long as my dose is not lower than 10g. I don't know why it works for emotional numbness, but another guy also got consistent benefits from 1000 mg Allicin regarding his post-antidepressant emotional numbness. Allicin is also a sulfur compound. He attributes it to, perhaps, sulfur's effect on the hypothalamus, which is a critical regulator of emotions. Maybe MSM works in a similar way.

The only side effect I notice from MSM is tachycardia and a mild anxiogenic effect, so far.

[ThreeKings12341]

 

thx Diesel , would u be so kind and tell me the product u are using? pls

 

how are the effects today?

I'm using a locally produced one. You should find something that contains at least 5g per pill, or instead go for bulk.

The effects are still consistent as long as my dose is not lower than 10g. I don't know why it works for emotional numbness, but another guy also got consistent benefits from 1000 mg Allicin regarding his post-antidepressant emotional numbness. Allicin is also a sulfur compound. He attributes it to, perhaps, sulfur's effect on the hypothalamus, which is a critical regulator of emotions. Maybe MSM works in a similar way.

The only side effect I notice from MSM is tachycardia and a mild anxiogenic effect, so far.

 

 

ah you mean the member "HIP", yes i tried allicin. didnt work unfortunately...

[dopaminerush]

You should do some fast running cardio + weight training3 times a week. It can speed up brain recovery and has antidepressant effect on itself. Stop being sedentary. 

 

May be you have high interleukin-6 levels and inflamatory markers. This thing is causing artiriths but at the same time depression. just type ''depression interleukin 6'' to google.

 

If you are overweight, lose weight. change you bodies inflamatory balance. take fish oil eat less inflamator fats.

 

 

try 800mg ibuprofen  once if it works high dose fish oil can work for your depression.

 

did you tried probiotics ? 

have a look at evidence :

https://mentalhealth...s-modification/

 

this is arthiritis drug (il6 blocker) augmentation study for depression

https://clinicaltria...how/NCT02660528

the thing is very expensive but give idea about what can be going on.

[ThreeKings12341]

hey

any updates on msm? hows the emotional numbness?

[Nate-2004]

From what I've read, at least from a single study, MSM can cause a notable reduction in exercise induced oxidation. I'm not sure if that's actually a good thing though, because it is the oxidation that creates the beneficial stress response that's needed from exercise. Otherwise there's really no point in exercising. 

 

http://www.ncbi.nlm....pubmed/21899544

 

Also, it's suspected that the benefits come more so from addressing a sulfur deficiency than anything else, and glucosamine sulfate as well as NAC can address these issues.

Edited by Nate-2004, 27 February 2018 - 04:32 PM.

[Diesel]

hey

any updates on msm? hows the emotional numbness?

My emotions are still noticeable and my libido has returned by at least 25%. I managed to masturbate but I do seem to get post-orgasmic illness symptoms (never had that in my life before SSRIs). I get bad depression that lasts for a day and the following day my body and joints hurt.

Emotions-wise, I woke up with a song in my head today that I hummed to and felt nostalgic, which is something I hadn't experienced in over a year. Overall, MSM is doing something but time will only tell if any permanent effects will be induced.

[Diesel]

I felt like I no longer need Rasagiline and LDN anymore, so I stopped taking them a couple of days ago. Since MSM gives me some energy (and anxiety), I also lowered my Metformin dose to 1g which is the sweet spot now. Instead of Melatonin, which seems to flare up my body inflammation, I've been taking a tiny dose of Baclofen (12.5 mg) for sleep.
 

My emotions always fade away some hours after dosing MSM, though. I tried 50 mg ginkgo extract with it yesterday and I got a rush of emotions so intense that certain music brought tears to my eyes. Ginkgo never worked before MSM (across all doses), but maybe now there's hope for cementing the pro-emotional 5HT1A upregulation effect. I have had not managed to cry for years before this, just for reference.

MSM + ginkgo biloba make me feel emotions despite feeling a bit anhedonic from Rasagiline withdrawal. I wonder how I will feel like once I get over this withdrawal a couple of weeks from now.

My current regimen looks like this now:
- MSM >5 g.
- Baclofen 12.5 mg.
- Ginkgo biloba extract (50 mg, still not fully decided - under experimentation).
- Nigella Sativa oil + fish oil for joint pain and body inflammation. (Better than LDN for me)
- Vitamins/minerals: Vitamin B1, B6, B12, D, C, magnesium, selenium, molybdenum and zinc.

Despite having at least 50% relief of complete emotional numbness, libido is still an issue. Once the withdrawals are over, I'll get testosterone, E2, DHEA, and progestrone tested out if my libido doesn't improve.

The current withdrawal symptoms I experience feel excitatory in nature. I bet Ginkgo doesn't help with that since it's a GABA-A subreceptors antagonist. But I'm willing to go along with it because having emotions again is so exciting I wouldn't want to miss having them again.

Edited by Diesel, 05 March 2018 - 04:39 AM.

[Galaxyshock]

I've read some bodybuilders taking up to 30 grams a day of MSM for deworming and other benefits. Because of the dramatic improvement in skin health etc. they describe it as "poor man's HGH".

[Diesel]

Update: 
I think Ginkgo biloba initially enhanced MSM's effect on my emotions through GABA-A subreceptor antagonism and 5HT1A presynaptic agonism/sensitization, causing more NMDA activation. However, recently it's doing the opposite; nullifying MSM's pro-emotional effect entirely. This is most likely due to its glycine antagonism and downregulation, causing frontal lobe disruption as seen in negative symptoms of schizophrenia (emotional numbness, etc).

I quite like Ginkgo's effect on 5HT1A (sensitization), so I have to find something that does the same thing without glycine antagonism. SJW (hypericum perforatum) does the same, but it also upregulates 5HT2 receptors which is very bad.

Maybe I should just stick to MSM monotherapy for emotions until I can get my hands on Berberine.

Edited by Diesel, 14 March 2018 - 08:32 AM.

[Diesel]

SJW upregulates only the postsynaptic 5HT1A receptors, not the presynaptic ones apparently.

Ethanol can induce presynaptic 5HT1A supersensitivity in mice.
h ttps://www.ncbi.nlm.nih.gov/pubmed/19094059

[ThreeKings12341]

thx for the updates

 

ginko biloba made me depressed,

 

why do u wanna take beberine (i also have this at home but havent taken it..- bought this cuz of a book)

 

 

[Diesel]

thx for the updates

 

ginko biloba made me depressed,

 

why do u wanna take beberine (i also have this at home but havent taken it..- bought this cuz of a book)

Berberine is a presynaptic 5HT1A agonist and postsynaptic 5HT1A antagonist, which would be extremely helpful for PSSD. It's also a PDE5 inhibitor and on top of that it can reduce PDE5 mRNA expression, so it would improve erectile dysfunction issues. It's an antagonist at 5HT4 which would improve vasodilation.

Berberine + Ginkgo (to prevent presynaptic 5HT1A desensitization) would, in theory, fix PSSD. Chronic SSRI intake might also decrease SERT expression, so something that depletes serotonin level can be needed if those 2 aren't enough. (i.e. Shilajit, Feverfew or Chasteberry/Vitex).

The only bad thing about Ginkgo is the glycine antagonism, which can be counteracted by taking sarcosine, D-aspartic acid, or a GlyT inhibitor. I have no access to any of those. I think Berberine + Ginkgo + Shilajit + Sarcosine would be the gold standard for PSSD treatment, in my opinion.

To enhance NMDA receptor function even further and lower prolactin release, we might want to block 5HT3, 5HT2A, 5HT2C, 5HT1B, 5HT1D, and 5HT2B as well. I think it's an overkill and not needed to do this, but Yohimbine can block 1B, 1D and 2B (to a lesser extent). Ginger is 5HT3/2B antagonist.

If one was taking SSRI to combat depression, then maybe there is a low-grade neuroinflammation going on or a high 5HT2 receptor density. 5HT2 receptors, unlike other receptors, downregulate in response to both agonism and inverse agonism, but most ligands are not selective and have a very bad pharmacological profile, such as H1 inverse agonism, which would downstream inhibit NMDA receptors. So, I wouldn't touch those receptors unless selective ligands become accessible.

For inflammation, I found nigella sativa oil + omega 3 to be very effective. Nigella sativa inhibits IL-6, IL-1b, and TNF-a but at high dose it contains a lot of omega 6, and to keep that in balance omega 3 should be taken. Omega 3 will also help downregulate 5HT2C receptors somewhat. A healthy lifestyle would help a lot in keeping your sex hormones in normal range.

Make sure you get enough vitamin D, C, B12, folate, zinc, selenium, and magnesium. I also like taking Melatonin for increased 5HT1A receptor sensitivity and improved sleep and oxytocin release, but take no more than 0.5 mg, as high doses are shown to decrease oxytocin release which would be bad for blunted affect. Melatonin can make some people depressed though, and it can increase IL-6 release so would be bad for patients suffering from certain autoimmune disorders as that would aggravate them.

This is all I know regarding PSSD (aside from a possible GIRK response desensitization, but it's not possible to target that at this time).

If you want references to the aforementioned mechanisms of action, please check Area-1255's blogspot. It contains a wealth of information regarding PSSD and is backed by references. Cheers!

Edited by Diesel, 15 March 2018 - 08:41 PM.

[ThreeKings12341]

thx very interesting!

i actually have black seed oil, sarcosine, shiljait (from nd), might try it out together ..

unfortunately i have no clue about things like 5ht, i wish i could understand that all...

[ThreeKings12341]

hey any updates?

[Diesel]

hey any updates?

It still works but it doesn't leave any permanent effects. It's impractical as I keep needing to redose many times a day.

The best thing that worked consistently for my PSSD is probably daily low-dose (120 mg) dextromethorphan, but chronic DXM intake can cause bromide toxicity. DXM is a GIRK antagonist at a low dose, so perhaps it causes re-sensitization of the 5HT1A->GIRK response. It has so many mechanisms of action, so it's exceedingly difficult to pinpoint how it benefits blunted affect and PSSD.

The beneficial effect on blunted affect and libido last for 2-3 days after stopping the DXM intake. I've experienced great libido boost and emotions when DXM is out of my system. The libido boosts is probably due to NMDA upregulation / rebound sensitization. Hell, maybe its sigma-1 agonism also contributes.

Please note that while under the effect of DXM, I actually experience even more blunted affect and loss of libido, which is normal given it's dissociative effect. The benefits I experience from DXM are felt after its out of my system actually. High dose DXM is useless as when it wears off, I end up with profound anhedonia, so only low-dose DXM works.

The problem with DXM? cognitive dysfunction and memory problems even from chronic low dose intake. I tried to join pssdforum website in order to share my opinion on why DXM works, and try to replicate the results using a safe drug that doesn't cause cognitive dysfunction or bromide toxicity, but I can't create an account there (I don't receive the activation email) and the admins ignore my emails when I ask them to fix this. So, I can't know for sure why DXM helps or whether these results can be replicated by other people suffering from PSSD.

Edited by Diesel, 30 March 2018 - 07:57 PM.

[ThreeKings12341]

thx for the update ! , at least it still works. yes ive heard of dxm  and its benefits but i never really tried it out.. its dangerous so ill leave that out.. maybe one time to try to know how it feels like..

[Diesel]

thx for the update ! , at least it still works. yes ive heard of dxm  and its benefits but i never really tried it out.. its dangerous so ill leave that out.. maybe one time to try to know how it feels like..

You are right, at least it keeps working. I hope I don't get tolerant to its effects.

[Diesel]

Small update:
Liquorice seems to amplify MSM's effect on PSSD. Potent synergism here. A short googling session revealed that some PSSD victims also found liquorice helpful, but it quickly loses its effect. Perhaps this is mediated via liquorice's mineralocorticoid activity. I don't find that strange, since those receptors are present on the hippocampus and play a role in its function.

I read that Piracetam works through augmenting the mineralocorticoid receptors. How about Piracetam + liquorice then to prevent tolerance?

[ThreeKings12341]

this  http://www.dr-bob.or...gs/972934.html u mean?

[Diesel]

this  http://www.dr-bob.or...gs/972934.html u mean?

This, and other anecdotes. However, its emotional-restoring ability took 2 days only for me and it was largely accidental and unanticipated so we can rule out placebo.

Edited by Diesel, 03 April 2018 - 06:35 PM.

[ThreeKings12341]

 took it a week didnt do much, ill do it 2 months in future again.. i have low cortisol anyway from saliva test...

 

ps: would actually really appreciate it if u could link me the other anecdotes of licoricee root pls

Edited by ThreeKings12341, 03 April 2018 - 09:34 PM.

[Diesel]

 took it a week didnt do much, ill do it 2 months in future again.. i have low cortisol anyway from saliva test...

 

ps: would actually really appreciate it if u could link me the other anecdotes of licoricee root pls

Sorry for not updating you; after taking licorice I've become extremely fatigued I'm sleeping most of the days. Although licorice improves my fatigue and low libido temporarily, when it wears off these symptoms become much, much worse than baseline. I need to keep redosing licorice just to be able to stay awake now.

This suggests that I have a major problem either with my HPA axis response and/or with cortisone/cortisol metabolism, and licorice has made it more apparent. Perhaps past SRI intake has caused blunted HPA axis response? Therefore, I need to have some blood tests done soon (ACTH stimulation test), but I wonder if licorice intake would interfere with the result.

I'm so tired.

[ThreeKings12341]

hey how u feeling now ?

 

ps: have u got these licoricee stories maybe please?